Coumarins in hypertension management: from vascular signaling pathways to clinical perspectives

Hypertension remains a leading modifiable risk factor for cardiovascular morbidity and mortality worldwide. Beyond conventional pharmacotherapy, growing interest has focused on bioactive natural compounds with vascular-protective properties. Coumarins, a diverse class of plant-derived benzopyrones, have emerged as potential modulators of blood pressure through their effects on endothelial function, oxidative stress, inflammation, and vascular remodeling. This review aimed to critically synthesize current evidence on the role of coumarins in hypertension management, integrating mechanistic insights, preclinical findings, pharmacokinetic considerations, and available clinical data. A structured analysis of experimental and clinical literature was conducted, emphasizing vascular signaling pathways implicated in hypertension. Data from in vitro studies, animal models of elevated blood pressure, observational cohorts, and randomized interventions were evaluated, with particular attention to nitric oxide bioavailability, reactive oxygen species modulation, inflammatory cytokine regulation, smooth muscle cell proliferation, and autonomic control mechanisms. Preclinical studies consistently demonstrate that several coumarin derivatives enhance endothelial-dependent vasodilation, restore nitric oxide signaling, reduce oxidative stress via NADPH oxidase inhibition, attenuate pro-inflammatory cytokine expression, and limit vascular smooth muscle cell proliferation. In hypertensive animal models, these effects translate into improved baroreflex sensitivity and reduced blood pressure. Observational studies and limited clinical trials suggest an inverse association between dietary coumarin intake and blood pressure levels; however, randomized evidence remains scarce and occasionally inconclusive. Coumarins exhibit multifaceted vascular-protective properties that support their potential as adjunctive agents in hypertension management. While mechanistic and preclinical data are compelling, robust, well-designed clinical trials are required to clarify efficacy, safety, optimal dosing, and patient stratification strategies before definitive therapeutic recommendations can be made.